Can Orgovyx (relugolix) cause hypothyroidism?

Orgovyx (Relugolix) and Hypothyroidism

Orgovyx (relugolix) has not been directly associated with causing hypothyroidism based on the available evidence. While many medications can affect thyroid function, there is no specific evidence linking Orgovyx to hypothyroidism in the current literature.

Mechanism of Action and Known Side Effects

Orgovyx (relugolix) is a gonadotropin-releasing hormone (GnRH) antagonist approved for the treatment of advanced prostate cancer. Unlike LHRH agonists, it works by:

• Directly blocking GnRH receptors
• Rapidly suppressing testosterone without initial surge
• Allowing for quicker testosterone recovery upon discontinuation 1

The most commonly reported adverse events associated with Orgovyx include:

• Hot flushes
• Fatigue
• Asthenia
• Constipation
• Myalgia 2

Thyroid-Related Considerations

Medication Classes Known to Cause Hypothyroidism

Several medication classes are known to cause hypothyroidism through various mechanisms:

1. Tyrosine kinase inhibitors - Can cause primary hypothyroidism
2. Immune modulators (interferon, cytokines) - Can trigger immune-mediated thyroid dysfunction
3. Amiodarone - Well-documented thyroid effects
4. Lithium - Has important antithyroid effects 3, 4

However, GnRH antagonists like Orgovyx are not included in this list of medications with known thyroid effects.

Monitoring Recommendations

While not specifically for Orgovyx, general recommendations for medication monitoring include:

• Baseline thyroid function testing (TSH and free T4) before starting treatments that may affect thyroid function
• Regular monitoring of thyroid function during treatment with medications known to affect the thyroid 5

Clinical Implications

Differential Diagnosis of Hypothyroidism

If a patient on Orgovyx develops symptoms suggestive of hypothyroidism, consider:

1. Primary hypothyroidism - Characterized by elevated TSH and low free T4
2. Central hypothyroidism - Low/normal TSH with low free T4
3. Subclinical hypothyroidism - Elevated TSH with normal free T4 6

Management Approach

For patients on Orgovyx with suspected thyroid dysfunction:

1. Confirm with appropriate testing:

   • TSH and free T4 measurements
   • Repeat testing in 4-6 weeks if results are borderline 6

2. If hypothyroidism is confirmed:

   • Initiate levothyroxine replacement therapy
   • Monitor TSH levels every 6-8 weeks during dose titration
   • Target TSH within reference range (0.45-4.5 mIU/L) 6

Practical Considerations

In real-world experience with Orgovyx:

• Patient compliance is generally good (94% of days covered in available data)
• No major new safety signals have been observed, even in combination therapy
• Most patients who switched from other forms of ADT tolerated Orgovyx similarly or better 7

Conclusion

While thyroid dysfunction is a potential side effect of many medications, there is currently no evidence specifically linking Orgovyx (relugolix) to hypothyroidism. Clinicians should remain vigilant about monitoring for potential endocrine side effects with any medication, but hypothyroidism does not appear to be a significant concern with Orgovyx based on current evidence.